The proposed program represents a multidisciplinary investigation of the causes and treatment of mental retardation, involving clinical studies, neurological studies, genetic studies and biochemical studies. The clinical research endeavors will involve the patient population at the W.E. Fernald State School, Region III of the Commonwealth of Massachusetts and elsewhere. These will be focused primarily on inborn enzymatic errors of metabolism as well as chromosomal abberations. In addition to various metabolic studies with such patients, we shall be involved in identification of storage substrates in tissues and body fluids, utilization of skin fibroblasts and lymphocytes grown in culture, improved methodology for both homozygotes effected and heterozygote detection and hopefully for information ultimately useful for prevention and therapy. Lysosomal acid hydrolases will be extensively studied and purified. Related basic research will be concerned with cerebral lipid and steroidal hormone metabolism. A thorough and detailed understanding prior to a rational assessment of their functional role can be appreciated. Intelligent understanding of the diseases state caused by abnormal metabolism of these components is predicted upon such fundamental biochemical knowledge.